A low molecular weight, noncytotoxic species-independent inhibitor of lymphocyte division is released by metabolizing rat spleen cells into their culture supernatant. l. Large volumes of this supernatant will be produced and the low molecular weight inhibitor purified by molecular filtration, ion exchange, high pressure liquid and thin layer chromatography. 2. The active molecule will be characterized and its structure elucidated by functional group analysis, nuclear magnetic resonance, infrared, ultraviolet and mass spectroscopy. 3. Highly purified fractions will be screened for their effects on a panel of malignant human lymphoid cells from patients with leukemia and lymphoma. Utilizing a standard preparation of inhibitor and assays for both DNA synthesis and mitosis, dose-response curves will be used to compare its effects on malignant vs. normal lymphoid cells. 4. The mechanism of action will be investigated by determining its effects on a) the transmembrane transport of radiolabelled RNA and DNA nucleoside precursors, 2-deoxyglucose and L-leucine, b) the intracellular levels of cyclic AMP, and c) the cell cycle (using FMF analysis). 5. Its in vivo effects on the recurrent growth of murine lymphoid ascites tumors will be studied to provide an initial evaluation of its usefulness for chemotherapy of patients with lymphoid malignancies. 6. Potential binding or antagonism of the inhibitor by serum proteins and factors released by malignant lympoid cells will be investigated using the method of equilibrium dialysis.